Pancreatic ductal adenocarcinoma cells regulated the gemcitabine-resistance function of CAFs by LINC00460.

Pancreatic ductal adenocarcinoma (PDAC) is a highly fatal malignancy with extremely poor prognosis. Gemcitabine resistance is a major challenge in the treatment of PDAC. Here, we showed that LINC00460 was associated with the response to gemcitabine both in PDAC patients and PDAC-PDX. After knocking down LINC00460 in PDAC tumor cells, results of RNA sequencing followed by gene ontology analysis indicated that LINC00460 influenced the activity of growth factors and modified the extracellular matrix. FISH showed that LINC00460 is mostly located in the cytoplasm. Results of RNA pull-down, LC-MS/MS, RIP, and immunoblotting confirmed that LINC00460 could directly bind to PDAP1. Furthermore, we demonstrated that LINC00460 mediated the cellular communication of PDAC tumor cells and CAFs by PDAP1/PDGFA/PDGFR signaling pathway and regulated the gemcitabine-resistance function of CAFs, which could be reversed by treatment with a PDGFR inhibitor (crenolanib). PDAC-PDX tumors with lower expression of LINC00460 showed a better response to gemcitabine plus crenolanib treatment. Our finding supported the application of LINC00460 in precision medicine that uses gemcitabine plus crenolanib to treat PDAC with low expression of LINC00460.

Simultaneous heart valve replacement surgery and abdominal subtotal hysterectomy: case report.

A middle-aged woman with rheumatic heart disease, mitral valve prolapse and incompletely closed mitral valve medium, patent foramen ovale, merge multiple uterine fibroids, and moderate blood loss anemia underwent mitral valve replacement surgery with total abdominal hysterectomy under general anesthesia and cardiopulmonary bypass condition. The surgery was successful, and postoperative bleeding, blood clots, heart failure, and other related complications did not occur. Heart valve replacement surgery with the surgical treatment of uterine fibroids effectively improves the safety of surgical treatment for patients as well as reduces the patient's medical expenses and risk of secondary surgery and trauma.

[Preparation of Chitosan-modified Biochar and Its Adsorption Mechanism for Cd2+ in Aqueous Solution].

Chitosan-modified biochar （CBC） was prepared as a low-cost and highly efficient adsorbent for Cd2+ in aqueous solutions. Batch adsorption experiments were conducted to evaluate the adsorption performance. Characterization experiments with SEM-EDS， FTIR， and XPS were used to analyze the surface microstructure and chemical composition of the adsorbent. The results showed that the adsorption performance of CBC was remarkably improved by the introduction of surface functional groups （-OH， -C=O， and -NH2）. The pseudo-second-order kinetic model and Langmuir model were better for describing the kinetics and isotherms for Cd2+ adsorption onto CBC， indicating that the adsorption rate was determined by the active sites and controlled by monolayer chemisorption. The adsorption process was endothermic spontaneous， and the key mechanisms involved complexation， precipitation， cation exchange， and cation-π bonds. After five instances of adsorption-desorption cycles， the adsorption capacity of CBC for Cd2+ still remained above 80% of the initial adsorption capacity， indicating that CBC had a favorable recyclability. The current work embodies the concept of green chemistry， and the prepared chitosan-modified biochar was a promising adsorbent for the removal of Cd2+ in wastewater and soil.

Cabrol procedure and its modifications: a systematic review and meta-analysis.

BACKGROUND: The Cabrol procedure has undergone various modifications and developments since its invention. However, there is a notable gap in the literature regarding meta-analyses assessing it. METHODS: A systematic review and meta-analysis was conducted to evaluate the effectiveness and long-term outcomes of the Cabrol procedure and its modifications. Pooling was conducted using random effects model. Outcome events were reported as linearized occurrence rates (percentage per patient-year) with 95% confidence intervals. RESULTS: A total of 14 studies involving 833 patients (mean age: 50.8 years; 68.0% male) were included in this meta-analysis. The pooled all-cause early mortality was 9.0% (66 patients), and the combined rate of reoperation due to bleeding was 4.9% (17 patients). During the average 4.4-year follow-up (3,727.3 patient-years), the annual occurrence rates (linearized) for complications were as follows: 3.63% (2.79-4.73) for late mortality, 0.64% (0.35-1.16) for aortic root reoperation, 0.57% (0.25-1.31) for hemorrhage events, 0.66% (0.16-2.74) for thromboembolism, 0.60% (0.29-1.26) for endocarditis, 2.32% (1.04-5.16) for major valve-related adverse events, and 0.58% (0.34-1.00) for Cabrol-related coronary graft complications. CONCLUSION: This systematic review provides evidence that the outcomes of the Cabrol procedure and its modifications are acceptable in terms of mortality, reoperation, anticoagulation, and valve-related complications, especially in Cabrol-related coronary graft complications. Notably, the majority of Cabrol procedures were performed in reoperations and complex cases. Furthermore, the design and anastomosis of the Dacron interposition graft for coronary reimplantation, considering natural anatomy and physiological hemodynamics, may promise future advancements in this field.

Angiotensin receptor blockers retard the progression and fibrosis via inhibiting the viability of AGTR1+ CAFs in intrahepatic cholangiocarcinoma.

BACKGROUND: Intrahepatic cholangiocarcinoma (iCCA) is a highly lethal malignancy characterized by massive fibrosis and has ineffective adjuvant therapies. Here, we demonstrate the potential of angiotensin receptor blockers (ARBs) in targeting iCCA. METHODS: Masson's trichrome staining was used to assess the effect of ARBs in iCCA specimens, CCK8 and gel contraction assays in vitro and in xenograft models in vivo. RNA-seq and ATAC-seq were used for mechanistic investigations. RESULTS: Patients with iCCA who were administered ARBs had a better prognosis and a lower proportion of tumour stroma, indicating alleviated fibrosis. The presence of AGTR1, the ARBs receptor, is associated with a poor prognosis of iCCA and is highly expressed in tumour tissues and cancer-associated fibroblasts (CAFs). The ARBs strongly attenuated the viability of AGTR1+ CAFs in vitro and retarded tumour progression and fibrosis in xenograft models of co-cultured CAFs and iCCA cells. Still, they did not have a significant effect on AGTR1- CAFs. Moreover, ARBs decreased the secretion of AGTR1+ CAF-derived MFAP5 via the Hippo pathway, weakened the interaction between CAFs and iCCA cells, and impaired the aggressiveness of iCCA cells by attenuating the activation of the Notch1 pathway in iCCA cells. CONCLUSIONS: ARBs exhibit anti-fibrotic function by inhibiting the viability of AGTR1+ CAFs. These findings support using ARBs as a novel therapeutic option for targeting iCCA.

Comparison of stereotactic aspiration surgery and conventional treatment for primary brainstem haemorrhage.

OBJECTIVE: To explore the effect of stereotactic aspiration surgery and conventional treatment for primary brainstem haemorrhage. METHODS: The clinical data of 137 patients with primary brain stem haemorrhage (haematoma volume > 3 ml) from August 2014 to August 2022 at the First Hospital of Hebei Medical University were reviewed. Sixty-five patients were treated with stereotactic haematoma aspiration, and 72 patients were treated with conventional therapy. We followed up on patient survival after 30 days and the recovery of neurological function after 90 days. The recovery of neurological function was evaluated by the modified Rankin Scale (mRS) 90 days after treatment. The mortality and neurological recovery rates of the two treatments were compared and analysed. RESULTS: There was a significant difference in the 30-day mortality rate between the two treatment groups (p < 0.05). There was a significant difference in neurological function improvement after 90 days between the two treatment groups (P < 0.05). There was no significant difference between stereotactic aspiration and routine treatment in the prognosis of primary brainstem haemorrhage patients at 90 days after treatment (P > 0.05). CONCLUSION: Stereotactic aspiration surgery for primary brain stem haemorrhage can significantly reduce mortality and improve the neurological function of some patients.

SUMO specific peptidase 3 halts pancreatic ductal adenocarcinoma metastasis via deSUMOylating DKC1.

In the past few decades, advances in the outcomes of patients suffering from pancreatic ductal adenocarcinoma (PDAC) have lagged behind these gained in the treatment of many other malignancies. Although the pivotal role of the SUMO pathway in PDAC has been illustrated, the underlying molecule drivers have yet to be fully elucidated. In the present study, we identified SENP3 as a potential suppressor of PDAC progression through an in vivo metastatic model. Further studies revealed that SENP3 inhibited PDAC invasion in a SUMO system dependent fashion. Mechanistically, SENP3 interacted with DKC1 and, as such, catalyzed the deSUMOylation of DKC1, which accepted SUMO3 modifiers at three lysine residues. SENP3-mediated deSUMOylation caused DKC1 instability and disruption of the interaction between snoRNP proteins, which contributed to the impaired migration ability of PDAC. Indeed, overexpression of DKC1 abated the anti-metastasis effect of SENP3, and DKC1 was elevated in PDAC specimens and associated with a poor prognosis in PDAC patients. Collectively, our findings shed light on the essential role of SENP3/DKC1 axis in the progression of PDAC.

ACLP promotes activation of cancer-associated fibroblasts and tumor metastasis via ACLP-PPARγ-ACLP feedback loop in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with poor prognosis. Its fibrotic tumor microenvironment (TME) plays a crucial role in promoting tumor invasion and metastasis, which eventually leads to a dismal 5-year survival rate in PDAC patients. Aortic carboxypeptidase-like protein (ACLP) promotes tissue fibrosis in benign diseases. However, its role in cancer-associated fibrosis remains unelucidated. Here, we show that ACLP was mainly expressed in cancer-associated fibroblasts (CAFs) but not in cancer cells and highly expressed in PDAC tissues. High ACLP expression was correlated with poor overall survival. Moreover, ACLP expression in PDAC patients with liver metastases was higher than that in PDAC patients without liver metastases. By detecting activation marker expression and CAF contractility and motility, we found that ACLP promoted CAF activation in PDAC, leading to TME fibrosis. Furthermore, ACLP-activated CAFs could promote cancer cell invasion in vitro and tumor metastasis in vivo. Mechanistically, ACLP promotes the expressions of MMP1 and MMP3 in CAFs, thus promoting PDAC invasion and metastasis. Intriguingly, we identified an ACLP-PPARγ-ACLP feedback loop in PDAC CAFs. Abatement of this feedback loop might be a promising approach in CAF-targeting PDAC treatment.

Development and analysis of a comprehensive diagnostic model for aortic valve calcification using machine learning methods and artificial neural networks.

Background: Although advanced surgical and interventional treatments are available for advanced aortic valve calcification (AVC) with severe clinical symptoms, early diagnosis, and intervention is critical in order to reduce calcification progression and improve patient prognosis. The aim of this study was to develop therapeutic targets for improving outcomes for patients with AVC. Materials and methods: We used the public expression profiles of individuals with AVC (GSE12644 and GSE51472) to identify potential diagnostic markers. First, the R software was used to identify differentially expressed genes (DEGs) and perform functional enrichment analysis. Next, we combined bioinformatics techniques with machine learning methodologies such as random forest algorithms and support vector machines to screen for and identify diagnostic markers of AVC. Subsequently, artificial neural networks were employed to filter and model the diagnostic characteristics for AVC incidence. The diagnostic values were determined using the receiver operating characteristic (ROC) curves. Furthermore, CIBERSORT immune infiltration analysis was used to determine the expression of different immune cells in the AVC. Finally, the CMap database was used to predict candidate small compounds as prospective AVC therapeutics. Results: A total of 78 strong DEGs were identified. The leukocyte migration and pid integrin 1 pathways were highly enriched for AVC-specific DEGs. CXCL16, GPM6A, BEX2, S100A9, and SCARA5 genes were all regarded diagnostic markers for AVC. The model was effectively constructed using a molecular diagnostic score system with significant diagnostic value (AUC = 0.987) and verified using the independent dataset GSE83453 (AUC = 0.986). Immune cell infiltration research revealed that B cell naive, B cell memory, plasma cells, NK cell activated, monocytes, and macrophage M0 may be involved in the development of AVC. Additionally, all diagnostic characteristics may have varying degrees of correlation with immune cells. The most promising small molecule medicines for reversing AVC gene expression are Doxazosin and Terfenadine. Conclusion: It was identified that CXCL16, GPM6A, BEX2, S100A9, and SCARA5 are potentially beneficial for diagnosing and treating AVC. A diagnostic model was constructed based on a molecular prognostic score system using machine learning. The aforementioned immune cell infiltration may have a significant influence on the development and incidence of AVC.

Bioinformatics and Machine Learning Methods to Identify FN1 as a Novel Biomarker of Aortic Valve Calcification.

Aim: The purpose of this study was to identify potential diagnostic markers for aortic valve calcification (AVC) and to investigate the function of immune cell infiltration in this disease. Methods: The AVC data sets were obtained from the Gene Expression Omnibus. The identification of differentially expressed genes (DEGs) and the performance of functional correlation analysis were carried out using the R software. To explore hub genes related to AVC, a protein-protein interaction network was created. Diagnostic markers for AVC were then screened and verified using the least absolute shrinkage and selection operator, logistic regression, support vector machine-recursive feature elimination algorithms, and hub genes. The infiltration of immune cells into AVC tissues was evaluated using CIBERSORT, and the correlation between diagnostic markers and infiltrating immune cells was analyzed. Finally, the Connectivity Map database was used to forecast the candidate small molecule drugs that might be used as prospective medications to treat AVC. Results: A total of 337 DEGs were screened. The DEGs that were discovered were mostly related with atherosclerosis and arteriosclerotic cardiovascular disease, according to the analyses. Gene sets involved in the chemokine signaling pathway and cytokine-cytokine receptor interaction were differently active in AVC compared with control. As the diagnostic marker for AVC, fibronectin 1 (FN1) (area the curve = 0.958) was discovered. Immune cell infiltration analysis revealed that the AVC process may be mediated by naïve B cells, memory B cells, plasma cells, activated natural killer cells, monocytes, and macrophages M0. Additionally, FN1 expression was associated with memory B cells, M0 macrophages, activated mast cells, resting mast cells, monocytes, and activated natural killer cells. AVC may be reversed with the use of yohimbic acid, the most promising small molecule discovered so far. Conclusion: FN1 can be used as a diagnostic marker for AVC. It has been shown that immune cell infiltration is important in the onset and progression of AVC, which may benefit in the improvement of AVC diagnosis and treatment.

Posterior pericardiotomy to prevent new-onset atrial fibrillation after coronary artery bypass grafting: a systematic review and meta-analysis of 10 randomized controlled trials.

BACKGROUND: Atrial fibrillation (AF) is associated with adverse events after cardiac surgery. Multiple studies have reported that posterior pericardiotomy (PP) may be effective for preventing AF after coronary artery bypass grafting (CABG), but some conflicting results have been reported and the quality of evidence from previous meta-analyses has been limited. The present study aimed to systematically evaluate the safety and efficacy of PP for preventing AF after CABG in adults. METHODS: We conducted a quantitative meta-analysis of randomized controlled trials (RCTs) published before May 31, 2021. The primary outcome was AF after CABG under cardiopulmonary bypass. Secondary outcomes included early pericardial effusion, late pericardial effusion, pericardial tamponade, pleural effusion, length of hospital stay, length of intensive care unit (ICU) stay, pulmonary complications, intra-aortic balloon pump use, revision surgery for bleeding, and mortality. RESULTS: Ten RCTs with 1829 patients (910 in the PP group and 919 in the control group) were included in the current meta-analysis. The incidence of AF was 10.3% (94/910) in the PP group and 25.7% (236/919) in the control group. A random-effects model indicated that incidence of AF after CABG significantly lower in the PP group than in the control group (risk ratio = 0.45, 95% confidence interval 0.29-0.64, P < 0.0001). PP also effectively reduced the post-CABG occurrence of early pericardial effusion (RR = 0.28, 95% CI 0.15-0.50; P < 0.05), late pericardial effusion (RR = 0.06, 95% CI 0.02-0.16; P < 0.05), and pericardial tamponade (RR = 0.08, 95% CI 0.02-0.33; P < 0.05) as well as the length of ICU stay (weighted mean difference [WMD] = 0.91,95% CI 0.57-1.24; P < 0.05), while increasing the occurrence pleural effusion (RR = 1.51, 95% CI 1.19-1.92; P < 0.05). No significant differences length of hospital stay (WMD = - 0.45, 95% CI - 2.44 to 1.54, P = 0.66), pulmonary complications (RR = 0.99, 95% CI 0.71-1.39, P = 0.97), revision surgery for bleeding (RR = 0.84, 95% CI 0.43-1.63, P = 0.60), use of IABP (RR = 1, 95% CI 0.61-1.65, P = 1.0), or death (RR = 0.45, 95% CI 0.07-3.03, P = 0.41) were observed between the PP and control groups. CONCLUSIONS: PP may be a safe, effective, and economical method for preventing AF after CABG in adult patients.

Safety of Normothermic Cardiopulmonary Bypass in Pediatric Cardiac Surgery: A System Review and Meta-Analysis.

Objectives: Hypothermic cardiopulmonary bypass (HCPB) has been used successfully in cardiac surgery for more than half a century, although adverse effects have been reported with its use. Many studies on temperature management during CPB published to date have shown that normothermic CPB (NCPB) provides more benefits to children undergoing cardiac surgery. The present meta-analysis investigated the effect of NCPB on clinical outcomes based on results of randomized controlled trials and observational studies on pediatric cardiac surgery. Methods: Databases such as PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and Clinical Trials.gov were searched from inception to May 2021 to identify relevant studies published in English. Results: The present meta-analysis included 13 studies characterizing a total of 837 pediatric patients. The random effects model exhibited that the NCPB group had reduced revision for postoperative bleeding [odds ratio (OR): 0.11; 95% confidence interval (CI): 0.01-0.89; I 2 = 0%, P = 0.04], serum lactate 2-4 h after CPB (mean difference: -0.60; 95% CI: -1.09 to -0.11; I 2 = 82%, P = 0.02), serum creatinemia 24 h after CPB (mean difference: -2.73; 95% CI: -5.06 to -0.39; I 2 = 83%, P = 0.02), serum creatinemia 48 h after CPB (mean difference: -2.08; 95% CI: -2.78 to -1.39; I 2 = 0%, P < 0.05), CPB time (mean difference: -19.10, 95% CI: -32.03 to -6.18; I 2 = 96%, P = 0.04), and major adverse events (OR: 0.37; 95% CI: 0.15-0.93; Z = 2.12, P = 0.03) after simple congenital surgery compared with the HCPB group. Conclusion: NCPB is as safe as HCPB in pediatric congenital heart surgery. Moreover, NCPB provides more advantages than HCPB in simple congenital heart surgery.

Analysis of the curative effect and influencing factors of stereotactic aspiration in the treatment of primary brainstem haemorrhage.

Primary brainstem haemorrhage (PBH) is characterized by acute onset, rapid deterioration, many complications, and poor prognosis. Its treatment has been controversial. This study aimed to explore the clinical risk factors of postoperative survival and neurological function recovery of stereotactic aspiration in the treatment of PBH. The clinical data of 65 patients with severe brainstem haemorrhage from February 2019 to February 2020 in the First Hospital of Hebei Medical University were reviewed. All patients were treated with stereotactic haematoma aspiration. We determined the survival status of patients at 30 days after the operation and the recovery of neurological function at 90 days. The modified Rankin Scale score (mRS) was used to assess the survival status. The 30-day mortality rate was 23.1% (15 patients). The proportion of patients with good neurological recovery at 90 days after the operation was 32.3% (21 patients). According to the multivariate logistic regression analysis, the haematoma classification was an independent risk factor for postoperative survival (OR = 0.197, 95% CI: 0.016-0.385, p = 0.046) and recovery of neurological function 90 days after surgery (OR = 0.019, 95% CI: 0.001-0.267, p = 0.003). The haematoma classification is an independent risk factor for 30-day mortality and recovery of neurological function 90 days after surgery. Massive and basal-tegmental haematomas were associated with higher mortality. The prognosis of patients with unilateral and bilateral tegmental haematoma was better than that of patients with other haematoma types.

Prevalence of Congenital Heart Disease Amongst Schoolchildren in Southwest China.

OBJECTIVE: To investigate the prevalence and risk factors of congenital heart disease in Yunnan, China which has diverse ethnic groups. METHODS: This cross-sectional study enrolled 244,023 children from 2010 to 2015. To diagnose CHD, a conventional physical examination was used to screen suspicious cases, which were further confirmed by echocardiography. RESULTS: A total of 1695 children were diagnosed with CHD. The estimated prevalence was 6.94%. Atrial septal defects were the most common cardiac abnormalities. A higher prevalence of CHD was observed with preterm birth, low birth weight, maternal age ≥35 years, and high-altitude regions. The prevalence also showed differences between diverse ethnic groups. CONCLUSIONS: The prevalence of CHD in China may have ethnic differences.

Generation of human iPSC line from a patient with Tetralogy of Fallot, YAHKMUi001-A, carrying a mutation in TBX1 gene.

The human induced pluripotent stem cell (iPSC) line YAHKMUi001-A was derived from the dermal fibroblasts of a patient with Tetralogy of Fallot (TOF), with a mutation in the TBX1 gene (c.928G > A). The skin fibroblasts were obtained from a 4-year-old boy, and were infected with Sendai virus expressing the Yamanaka factors. The YAHKMUi001-A iPSC line expresses pluripotent stem cell markers, displays a normal karyotype, and has the capacity to differentiate into 3 germ layers. This cell line model can be a good tool to study the pathological mechanism of the TBX1 gene mutations associated with TOF.